Mount Sinai ADRC (Sano): Genetics and Genomics Core (Core F) ? Research Summary One hundred years ago dementing illnesses were classified based upon their clinical presentation and neuropathology. The promise of the twenty first century is that we will be able to classify these same diseases by the genetic cause or genetic risk factors, a classification based upon etiology not symptomatology. During the last three decades many genes have been shown to cause autosomal dominant forms of early onset dementing illnesses. These rare disorders have provided enormous insight into the pathogenesis of more common variants of the same diseases. In 1993, a polymorphism in the apolipoprotein E (APOE) gene was identified as the first genetic risk factor for AD. A dose-dependent effect of the APOE4 allele has now become an important variable in all studies of AD. During the last ten years genome-wide association studies and next generation sequencing studies have begun to identify many novel risk factors for AD. The goal of the Genetics and Genomics Core of the ISMMS ADRC is to provide genetic data and biospecimens on all ADRC participants. We will obtain blood samples on ADRC participants. One blood sample will be sent to NCRAD, where it will be available to the entire community and will be included in national AD Genetics initiatives such as ongoing genome-wide association studies (GWAS) and whole genome/exome sequencing projects. The second tube will be retained locally. For DNA. Plasma and APOE genotype will also be available on all ADRC participants. Many participants will also have GWAS, exome array and/or whole exome/genome sequence data through national and international initiatives and ADRC affiliated projects. This data will be stored in the master ISMMS ADRC database and provided to investigators upon request. The Core will support projects and other cores as well as ADRC affiliated ageing and dementia projects. New in this application, we will begin to bank PBMCs and pilot plasma biomarker collection to enable novel biomarker programs in peripheral tissues.